Tetracalcium phosphate (TTCP) having calcium phosphate whisker on surface and process for preparing the same

ABSTRACT

A tetracalcium phosphate (TTCP) particle for use in preparing a fast-setting, bioresorbable calcium phosphate cement is disclosed. The TTCP particle has a basic calcium phosphate whiskers on a surface thereof; the basic calcium phosphate whiskers having a Ca/P molar ratio greater than 1.33, and having a length up to about 5000 nm and a width up to about 500 nm. The basic calcium phosphate whiskers are substantially free of a hydroxyapatite phase and mainly composed of TTCP phase.

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] The present application is a continuation-in-part application ofU.S. patent application Ser. No. 10/607,023, filed Jun. 27, 2003, whichis a continuation-in-part application of U.S. patent application Ser.No. 10/414,582, filed Apr. 16, 2003, which is a continuation-in-partapplication of U.S. patent application Ser. No. 09/615,384, filed Jul.13, 2000, now abandoned, which is a continuation-in-part application ofU.S. patent application Ser. No. 09/351,912, filed Jul. 14, 1999, nowU.S. Pat. No. 6,379,453B1. The above-listed applications are commonlyassigned with the present invention and the entire contents of which areincorporated herein by reference.

BACKGROUND OF THE INVENTION

[0002] 1. Field of the Invention

[0003] The present invention relates to a tetracalcium phosphate (TTCP)for producing fast-setting, bioresorbable calcium phosphate cements(CPC), and in particular, to a tetracalcium phosphate having whiskers onthe surface thereof for producing fast-setting, bioresorbable CPC havinga high initial strength.

[0004] 2. Description of the Related Art

[0005] U.S. Pat. No. 6,379,453B1 which is commonly assigned with thepresent invention discloses a process for producing a fast-setting,bioresorbable calcium phosphate cement comprising the following steps:obtaining a powder mixture from at least one calcium phosphate selectedfrom the group consisting of Ca₄(PO₄)₂O, CaHPO₄.2H₂O, CaHPO₄,Ca₈H₂(PO₄)_(6 .5)H₂O, alpha-Ca₃(PO₄)₂, beta-Ca₃(PO₄)₂, Ca₂P₂O₇,Ca₂H₂P₂O₈, wherein the molar ratio of Ca to P in the mixture is roughlybetween 1 and 2; mixing the powder mixture in a phosphate-containingsolution to obtain a powder/solution mixture having a concentration ofless than 4 g powder mixture per ml solution; immediately heating thepowder/solution mixture to a temperature of roughly 50° C.-350° C. toobtain a powder containing uniformly distributed submicron-sized apatitecrystals; and mixing the apatite crystal-containing powder in aphosphate ion-containing solution to obtain a fast-setting,bioresorbable calcium phosphate cement.

SUMMARY OF THE INVENTION

[0006] An extensive study on the preparation of the fast-setting,bioresorbable calcium phosphate cement disclosed in U.S. Pat. No.6,379,453B1 has been conducted by the same inventors and theirco-workers, and found that a fast-setting, bioresorbable CPC having ahigh initial strength can be prepared from a unique calcium phosphate,tetracalcium phosphate (Ca₄(PO₄)₂O, TTCP) particle having basic whiskersor fine crystals on the surface thereof, wherein said basic whiskers orfine crystals have a Ca/P ratio greater than 1.33. Therefore an objectof the invention is to provide such a unique TTCP particle. Anotherobject of the present invention is to provide a process for preparingsaid unique TTCP particle. A further object of the present invention isto provide a fast-setting, bioresorbable CPC calcium phosphate cementprepared from said unique TTCP particle.

[0007] The invention accomplishes the above object by providing atetracalcium phosphate (Ca₄(PO₄)₂O, TTCP) particle having basic calciumphosphate whiskers on a surface of said TTCP particle; said basiccalcium phosphate whiskers having a length up to about 5000 nm and awidth up to about 500 nm, and preferably, a length from about 1 nm toabout 2000 nm and a width from about 1 nm to about 200 nm. Said basiccalcium phosphate whiskers have a Ca/P molar ratio greater than 1.33,and preferably greater than 1.35 and less than 4.0. Said basic calciumphosphate whiskers have a non-stoichiometric chemical composition.Further, said basic calcium phosphate whiskers are substantially free ofa hydroxyapatite phase, and comprises TTCP as a major phase.

BRIEF DESCRIPTION OF THE DRAWINGS

[0008]FIGS. 1A to 1C are related to microstructure and diffractionpattern of calcium phosphate whiskers grown on TTCP surface according tothe present invention, wherein (a) bright field image of whiskers; (b)electron diffraction pattern of whiskers; and (c) interpretation of thediffraction pattern.

[0009]FIG. 2 shows XRD patterns, wherein (a) TTCP without whiskertreatment; (b) TTCP with whisker treatment in (NH₄)₂HPO₄ for 5 minutes;and (c) CPC prepared from whisker-treated TTCP powder immersed in Hanks'solution for 24 hours.

DETAILED DESCRIPTION OF THE INVENTION

[0010] The present invention discloses a process for preparing atetracalcium phosphate (TTCP) powder comprising TTCP particlescomprising basic calcium phosphate whiskers on surfaces of said TTCPparticles, said process comprising the following steps:

[0011] a) mixing a TTCP powder with a whisker-inducing solution so thatbasic calcium phosphate whiskers start to grow on surfaces of TTCPparticles of said TTCP powder;

[0012] b) terminating the growth of said calcium phosphate whiskers bydrying the whisker-inducing solution in the mixture, so that saidcalcium phosphate whiskers have a length up to about 5000 nm and a widthup to about 500 nm, and preferably, a length from about 1 nm to about2000 nm and a width from about 1 nm to about 200 nm, said basic calciumphosphate whiskers have a Ca/P molar ratio greater than 1.33, preferablygreater than 1.35 and less than 4.0, and said basic calcium phosphatewhiskers have a non-stoichiometric chemical composition, preferably saidbasic calcium phosphate whiskers are substantially free of ahydroxyapatite phase, and comprises TTCP as a major phase.

[0013] Optionally, at least one additive selected from the groupconsisting of sodium phosphate (Na₃PO₄), disodium hydrogen phosphate(Na₂HPO₄), sodium dihydrogen phosphate (NaH₂PO₄), disodium hydrogenphosphate dodecahydrate (Na₂HPO₄.12H₂O), disodium hydrogen phosphateheptahydrate (Na₂HPO₄.7H₂O), sodium phosphate dodecahydrate(Na₃PO₄.12H₂O), orthophosphoric acid (H₃PO₄), calcium sulfate (CaSO₄),Ca₄(PO₄)₂O, CaHPO₄.2H₂O, CaHPO₄, Ca₈H₂(PO₄)₆.5H₂O, alpha-Ca₃PO₄)₂,beta-Ca₃(PO₄)₂, Ca₂P₂O₇, and Ca₂H₂P₂O₈, (NH₄)₃PO₄, (NH₄)₂HPO₄, and(NH₄)H₂PO₄ together with said TTCP particles are mixed with thewhisker-inducing solution in step a).

[0014] Optionally, said drying in step b) is carried out by heating themixture resulting from step a) at a temperature less than about 1000° C.Preferably, said drying in step b) comprises separating the mixtureresulting from step a), and heating the separated powder at atemperature of about 50 to 500° C.

[0015] The heating includes (but not limited to) the conventionaloven/furnace heating, resistance heating, infrared heating, microwaveheating, electron beam heating, ion beam heating, laser beam heating andplasma heating. Preferably said heating is conducted in vacuum, inertatmosphere or air atmosphere.

[0016] The whisker-inducing solution in step a) may be an acidic aqueoussolution, a basic aqueous solution, an organic solvent or asubstantially pure water. The acidic aqueous solution may contain atleast one Ca or P source, or is free from Ca and P. The acidic aqueoussolution can be selected from the group consisting of nitric acid(HNO₃), hydrochloric acid (HCl), phosphoric acid (H₃PO₄), carbonic acid(H₂CO₃), sodium dihydrogen phosphate (NaH₂PO₄), sodium dihydrogenphosphate monohydrate, sodium dihydrogen phosphate dihydrate, potassiumdihydrogen phosphate (KH₂PO₄), ammonium dihydrogen.phosphate (NH₄H₂PO₄),malic acid, acetic acid, lactic acid, citric acid, malonic acid,succinic acid, glutaric acid, tartaric acid, oxalic acid and theirmixture.

[0017] The basic aqueous solution for use as the whisker-inducingsolution in the method of the present invention may contain at least oneCa or P source, or is substantially free from Ca and P. The basicaqueous solution may be selected from the group consisting of ammonia,ammonium hydroxide, alkali metal hydroxide, alkali earth hydroxide,disodium hydrogen phosphate (Na₂HPO₄), disodium hydrogen phosphatedodecahydrate, disodium hydrogen phosphate heptahydrate, sodiumphosphate dodecahydrate (Na₃PO₄.12H₂O), dipotassium hydrogen phosphate(K₂HPO₄), potassium phosphate tribasic (K₃PO₄), diammonium hydrogenphosphate ((NH₄)₂HPO₄), ammonium phosphate trihydrate ((NH₄)₃PO₄.3H₂O),sodium bicarbonate (NaHCO₃), and their mixture.

[0018] Preferably, said whisker-inducing solution in step a) is a basicaqueous solution. More preferably, said basic aqueous solution is adiammonium hydrogen phosphate ((NH₄)₂HPO₄), Na₂HPO₄, or K₂HPO₄ aqueoussolution. A suitable diammonium hydrogen phosphate ((NH₄)₂HPO₄) aqueoussolution has a concentration of at least 5 wt %, preferably 10-60 wt %,based on the weight of said solution, and the mixing of said TTCP powderwith this diammonium hydrogen phosphate ((NH₄)₂HPO₄) aqueous solution instep a) is in a ratio of less than about 10 g powder per ml solution,preferably less than about 5 g powder per ml solution. In one of thepreferred embodiment of the present invention, said concentration isabout 33 wt %, and the mixing ratio is about 1 gm TTCP per 13 mlsolution.

[0019] The present invention also discloses a calcium phosphate cement(CPC) powder comprising the TTCP powder of the present invention.

[0020] The following examples are intended to demonstrate the inventionmore fully without acting as a limitation upon its scope, since numerousmodifications and variations will be apparent to those skilled in thisart.

[0021] TTCP Preparation

[0022] The TTCP powder was fabricated in-house from the reaction ofdicalcium pyrophosphate (Ca₂P₂O₇) (Sigma Chem. Co., St. Louis, Mo., USA)and calcium carbonate (CaCO₃) (Katayama Chem. Co., Tokyo, Japan) usingthe method suggested by Brown and Epstein [Journal of Research of theNational Bureau of Standards—A Physics and Chemistry 6 (1965) 69A 12].

[0023] TEM Examination

[0024] A Hitachi Model-HF2000 200 kV field emission transmissionelectron microscope (TEM) equipped with a Noran Vayager Model 1000energy dispersive spectroscopy (EDS) system was used for the study. Theaperture size for microchemical analysis (Ca/P ratio) is 15 nm.

EXAMPLE 1 Whisker-Inducing Treatment of TTCP Particles Treated inPhosphate-Containing Basic Solution

[0025] Ca₄(PO₄)₂O (TTCP) powder as synthesized was sieved with a #325mesh. The sieved powder has an average particle size of about 10 μm. Anaqueous solution of diammonium hydrogen phosphate was prepared bydissolving 20 g of diammonium hydrogen phosphate, (NH₄)₂HPO₄, in 40 mldeionized water. The resulting solution had a pH value of 8.02. To theTTCP powder the basic aqueous solution of diammonium hydrogen phosphatewas added according to the ratio of 1 gm TTCP/13 ml solution. The TTCPpowder was immersed in the basic aqueous solution for various periods oftime of 1 minute, 5 minutes and 10 minutes, and filtered rapidly with avacuum pump again. The resulting powder cake was dried in an oven at 50°C. The dried powder was dispersed in ethanol with supersonication. Adrop of the dispersion was dripped on a single-side carbon sieve of #325mesh having a diameter of 3 mm, and left dry to obtain a specimen coatedwith a thin carbon film for electrical conductivity for TEM examination.The microchemical analysis (Ca/P ratio) results of ten specimens (P1 toP10) for each treat time are shown in Table 1. TABLE 1 Whisker WhiskerTreat Ca/P width length time P1 P2 P3 P4 P5 P6 P7 P8 P9 P10 Avg. SD*(nm) (nm)  1 min 1.20 1.30 1.26 1.14 1.12 1.03 1.22 1.19 1.14 1.25 1.190.08 <50 <100  5 min 1.85 1.61 1.35 1.76 1.40 1.52 1.63 1.53 1.35 1.381.54 0.17 <100 <300 10 min 3.81 3.20 1.78 1.74 1.80 1.38 1.61 1.81 2.011.63 2.08 0.78 <100 <300

[0026]FIG. 1 represents a typical microstructure of the calciumphosphate whiskers grown on TTCP surface under such condition. FIG. 1Ais a bright-field image showing the whiskers are substantiallyradial-oriented and the majority of which have lengths<300 nm andwidths<100 nm; FIG. 1B is a typical electron diffraction pattern of suchwhiskers. The dotted-ring pattern is a direct result of the diffractionof numerous nano-sized whiskers; FIG. 1C is the indexing/interpretationof the diffraction pattern, which clearly shows that every ring matchesa certain crystallographic plane of TTCP phase, indicating the whiskershave a TTCP crystal structure. The absence of hydroxyapatite (HA) phase(100) ring (d=0.817 nm) in the diffraction pattern excludes thepossibility for the whiskers to have an apatite crystal structure underthis whisker treatment condition. It also can be seen from Table 1 thatbasic calcium phosphate whiskers have a Ca/P ratio other than 1.67, i.e.a non-stoichiometric chemical composition. The Ca/P ratio ofhydroxyapatite (HA) is 1.67. The results show that Ca/P ratio issensitive to the process condition (in this case, treating time).

EXAMPLE 2 Whisker-Inducing Treatment of TTCP Particles Treated inPhosphate-Containing Acidic Solution

[0027] The procedures of Example 1 were repeated except that the basicaqueous solution was changed to 1M phosphorus acid aqueous solutionhaving a pH of 0.8 and the immersion time was changed to 30 seconds. Theresults are shown in Table 2. TABLE 2 Whisker Whisker Treat Ca/P widthlength time P1 P2 P3 P4 P5 P6 P7 P8 P9 P10 Avg. SD* (nm) (nm) 30 sec3.73 2.0 2.28 1.41 2.65 1.43 1.77 1.89 1.65 1.54 2.04 0.71 <200 <600

EXAMPLE 3 Whisker-Inducing Treatment of TTCP Particles Treated inPhosphate-Free Basic Solution

[0028] The procedures of Example 1 were repeated except that the basicaqueous solution was changed to a basic aqueous NaOH solution having apH of 10.66 and the immersion time was changed to 30 seconds and 24hours. For the specimens treated for 30 seconds no whisker was observedon TTCP surface. The results for the treat time of 24 hours are shown inTable 3. TABLE 3 Whisker Whisker Treat Ca/P width length time P1 P2 P3P4 P5 P6 P7 P8 P9 P10 Avg. SD* (nm) (nm) 24 hr 1.90 2.19 2.80 3.40 1.472.05 1.53 1.63 1.42 2.03 2.04 0.63 <200 <600

EXAMPLE 4 Whisker-Inducing Treatment of TTCP Particles Treated inPhosphate-Free Acidic Solution

[0029] The procedures of Example 1 were repeated except that the basicaqueous solution was changed to 0.16M HCl aqueous solution having a pHof 0.8 and the immersion time was changed to 30 seconds, 10 minutes, onehour and 24 hours. For the specimens treated for 30 seconds no whiskerwas observed on TTCP surface. The results for the remaining treat timesare shown in Table 4. TABLE 4 Whisker Whisker Treat Ca/P width lengthtime P1 P2 P3 P4 P5 P6 P7 P8 P9 P10 Avg. SD* (nm) (nm) 10 min 1.61 1.921.40 1.52 1.52 1.59 0.20 <50 <100  1 hr 1.41 1.90 1.52 1.67 1.57 1.421.53 1.46 1.38 1.60 1.55 0.15 <100 <200 24 hr 2.65 1.53 1.61 1.77 1.522.23 1.36 1.83 1.44 2.09 1.80 0.41 <200 <600

EXAMPLE 5 Compressive Strength of CPC Prepared from the Whisker-GrownTTCP Particles

[0030] Ca₄(PO₄)₂O (TTCP) powder as synthesized was sieved with a #325mesh and has an average particle size of about 10 μm. To the sieved TTCPpowder a HCl aqueous solution having a pH of 0.8 was added according tothe ratio of 1 gm TTCP/13 ml solution. The sieved TTCP powder wasimmersed in the HCl solution for 12 hours, filtered rapidly and washedwith deionized water, and filtered rapidly with a vacuum pump again. Theresulting powder cake was dried in an oven at 50° C. The dried powderwas divided into halves, ground for 20 minutes and 120 minutesseparately, and combined. A setting solution of diammonium hydrogenphosphate was prepared by dissolving 20 g of diammonium hydrogenphosphate, (NH₄)₂HPO₄, in 40 ml deionized water. 100 g of the mixedground powder and 35 ml of the setting solution were well mixed to forma paste, which was then filled in molds to form specimens forcompression test. The specimens were removed from the molds 15 minutesafter the mixing, and soaked in a Hanks' solution. The soaked specimenswere removed from the Hanks' solution at various periods of soakingtime, and were immediately subjected to the compression test withoutdrying. The compression test was conducted according to a methodcommonly used in the literature. The cylindrical samples have a diameterof 6 mm and a length of 12 mm. Results: compressive strength is 27.4 MPafor the soaking time of 20 minutes, and 48 MPa for one-day soaking time.

EXAMPLE 6 Compressive Strength of CPC Prepared from the Whisker-GrownTTCP Particles

[0031] Ca₄(PO₄)₂O (TTCP) powder as synthesized was sieved with a #325mesh and has an average particle size of about 10 μm. To the sieved TTCPpowder the aqueous (NH₄)₂HPO₄ solution prepared in Example 1 was addedaccording to the ratio of 1 gm TTCP/13 ml solution. The sieved TTCPpowder was immersed in the (NH₄)₂HPO₄ solution for 5 minutes, filteredrapidly and washed with deionized water, and filtered rapidly with avacuum pump again. The resulting powder cake was dried in an oven at 50°C. The dried powder was ground 120 minutes to obtain a powder A. Theprocedures in Example 5 were repeated to obtain a powder B except thatthe dried powder was ground only for a period of 300 minutes. A mixedpowder of A and B in a ratio of 1:1 ratio was subjected to thecompression tests following the procedures recited in Example 5.Results: compressive strength is 26 MPa for the soaking time of 20minutes, and 42.8 MPa for one-day soaking time.

EXAMPLE 7 Compressive Strength of CPC Prepared form the Whisker-GrownTTCP Particles

[0032] The procedures in Example 5 were repeated except that the HClsolution was changed to the aqueous (NH₄)₂HPO₄ solution prepared inExample 1 and the soaking time was changed to 5 minutes. Results:compressive strength is 18.6 MPa for the soaking time of 20 minutes, and48.8 MPa for one-day soaking time.

EXAMPLE 8 Compressive Strength of CPC Prepared from the Whisker-GrownTTCP Particles

[0033] Ca₄(PO₄)₂O (TTCP) powder as synthesized was sieved with a #325mesh and ground for two hours. To the ground TTCP powder the powder Bprepared in Example 5 was added and mixed in a ratio of 1:1. Theresulting mixed powder was subjected to the compression tests followingthe procedures recited in Example 5. Results: compressive strength is19.7 MPa for the soaking time of 20 minutes, and 43.6 MPa for one-daysoaking time.

EXAMPLE 9 X-Ray Diffraction of Whisker-Treated TTCP Powder and ImmersedCPC Prepared from such TTCP

[0034] A TTCP powder was whisker-treated for 5 minutes according to theprocess described in Example 1. X-ray diffraction (XRD) was performedusing an X-ray diffractometer (Rigaku D-max IIIV, Tokyo, Japan) withNi-filtered CuKα radiation operated at 30 kV and 20 mA at a scanningspeed of 1° /min. The phases were identified by matching eachcharacteristic XRD peak with that compiled in JCPDS files.

[0035] Results: As indicated in FIG. 2, the XRD pattern of thewhisker-treated TTCP powder (b) is substantially identical to that ofTTCP as synthesized (a). The perfect match of every XRD peak position(diffraction angle) with the JCPDS data indicates that there is noadditional phase formed during the whisker treatment. 0.7 gwhisker-treated TTCP powder with 0.25 ml setting solution to form a CPCpaste. The setting solution was prepared by dissolving 20 g (NH₄)₂HPO₄in 40 ml deionized water. The CPC paste was filled in a cylindrical mold(12 mm in height and 6 mm in diameter), allowing hardening of the pasteto occur within the mold. After 15 minutes the hardened CPC sample wasremoved from the mold and immersed in a 37° C. Hanks' solution for 24hours. After removing from the Hanks' solution and drying, the CPCsample was ready for XRD analysis. After immersion in Hanks' solutionfor 24 hours, the XRD pattern (c) of the CPC shows a large amount of HAphase which has replaced TTCP as the dominant phase. At this time only asmall amount of TTCP remains. The result suggests that the CPC preparedfrom the whisker-treated TTCP powder of the invention can quicklytransform into HA (the major component of human bone), once implanted.

EXAMPLE 10 Setting Solution Prepared from (NH₄)H₂PO₄ and KOH

[0036] A TTCP powder was whisker-treated for 5 minutes according to theprocess described in Example 1. The resulting powder cake was dried inan oven at 50° C. The dried powder was ground for 120 minutes. A settingsolution was prepared by dissolving 13.2 g (NH₄)H₂PO₄ in 40 ml deionizedwater to obtain an initial solution having a pH value of 3.72, andadding KOH to the initial solution so that the pH value was adjusted to7.5. 100 g of the ground powder and 35 ml of the setting solution werewell mixed to form a paste for 1 minute, which was then filled in moldsto form specimens for compression tests following the procedures recitedin Example 5. Results: compressive strength is 9.6 MPa for the soakingtime of 20 min.

EXAMPLE 11 Setting Solution Prepared from (NH₄)H₂PO₄ and NaOH

[0037] The procedures in Example 10 were repeated except that the KOHwas changed to NaOH and the final pH value of the setting solution was7.8, and 20 ml of the setting solution was mixed with 100 g of theground powder. Results: compressive strength is 10.3 MPa for the soakingtime of 20 min.

EXAMPLE 12 Setting Solution Prepared from (NH₄)₂ HPO₄, NaH₂PO4.2H2O andK₂HPO₄

[0038] A TTCP powder was prepared following the procedures recited inExample 10. A setting solution was prepared by dissolving 7.5 g(NH₄)₂HPO₄, 2.5 g NaH₂PO₄.2H₂O and 5 g K₂HPO₄ in 40 ml deionized water.The final pH value of the setting solution was 7.56. 100 g of the groundpowder and 30 ml of the setting solution were well mixed to form a pastefor 1 minute, which was then filled in molds to form specimens forcompression tests following the procedures recited in Example 5.Results: compressive strength is 18.0 MPa for the soaking time of 20min.

EXAMPLE 13 Setting Solution Prepared from Na₂HPO₄.12H₂O, NaH₂PO₄.2H₂Oand (NH₄)₂ HPO₄

[0039] A TTCP powder was prepared following the procedures recited inExample 10. A setting solution was prepared by dissolving 3 gNa₂HPO₄.12H₂O, 3 g NaH₂PO₄.2H₂O and 7.5 g (NH₄)₂HPO₄ in 40 ml deionizedwater. The final pH value of the setting solution was 7.38. 100 g of theground powder and 30 ml of the setting solution were well mixed to forma paste for 1 minute, which was then filled in molds to form specimensfor compression tests following the procedures recited in Example 5.Results: compressive strength is 20.8 MPa for the soaking time of 20min.

EXAMPLE 14 Setting Solution Prepared from Phosphoric Acid and AmmoniaSolution

[0040] A TTCP powder was prepared following the procedures recited inExample 10. A setting solution was prepared by mixing 37.68 ml of 85 wt% phosphoric acid and 100 ml deionized water, and then 73.8 ml of 28 wt% ammonia solution. The final pH value of the setting solution was 7.0.100 g of the ground powder and 30 ml of the setting solution were wellmixed to form a paste for 1 minute, which was then filled in molds toform specimens for compression tests following the procedures recited inExample 5. Results: compressive strength is 23.4 MPa for the soakingtime of 20 min.

[0041] Although a “basic” whisker can be grown on TTCP surface byimmersion in a variety of solutions, the process should be carefullycontrolled. For example, when the solution contains a P source in theabsence of Ca, the immersion time should be long enough to grow a basicwhisker (an “acidic” whisker is grown at the early stage due to theexcess P ions in the solution). Yet the immersion time should not be toolong either to avoid the basic whisker's growing too large, that canlargely deteriorate the CPC properties.

[0042] On the other hand, when the solution does not contain P (e.g.,HCl), acidic whisker is never grown on the surface of TTCP particles.All the observed whiskers on TTCP particles at all stages are basic innature.

[0043] In addition to Ca/P ratio, the growth rate of a basic whisker isalso sensitive to such process parameters as the type, pH, temperatureand ion concentrations of the solution, to name a few.

[0044] Although the present invention has been described with referenceto specific details of certain embodiments thereof, it is not intendedthat such details should be regarded as limitations upon the scope ofthe invention except as and to the extent that they are included in theaccompanying claims. Many modifications and variations are possible inlight of the above disclosure.

What is claimed is:
 1. A tetracalcium phosphate (TTCP) particlecomprising basic calcium phosphate whiskers on a surface of said TTCPparticle; said basic calcium phosphate whiskers having a length up toabout 5000 nm and a width up to about 500 nm, said basic calciumphosphate whiskers having a Ca/P molar ratio greater than 1.33, and saidbasic calcium phosphate whiskers having a non-stoichiometric chemicalcomposition.
 2. The tetracalcium phosphate as defined in claim 1,wherein basic calcium phosphate whiskers have a length from about 1 nmto about 2000 nm and a width from about 1 nm to about 200 nm.
 3. Thetetracalcium phosphate as defined in claim 1, wherein said basic calciumphosphate whiskers have a Ca/P molar ratio from about 1.35 to about 4.0.4. The tetracalcium phosphate as defined in claim 1, wherein said basiccalcium phosphate whiskers are substantially free of a hydroxyapatitephase.
 5. The tetracalcium phosphate as defined in claim 4, wherein saidbasic calcium phosphate whiskers comprise tetracalcium phosphate as amajor phase.
 6. A process for preparing a tetracalcium phosphate (TTCP)powder comprising TTCP particles comprising basic calcium phosphatewhiskers on surfaces of said TTCP particles, said process comprising thefollowing steps: a) mixing a TTCP powder with a whisker-inducingsolution so that basic calcium phosphate whiskers start to grow onsurfaces of TTCP particles of said TTCP powder; b) terminating thegrowth of said calcium phosphate whiskers by drying the whisker-inducingsolution in the mixture, so that said calcium phosphate whiskers have alength up to about 5000 nm and a width up to about 500 nm, said basiccalcium phosphate whiskers have a Ca/P molar ratio greater than 1.33,and said basic calcium phosphate whiskers have a non-stoichiometricchemical composition.
 7. The process as defined in claim 6, whereinbasic calcium phosphate whiskers have a length from about 1 nm to about2000 nm and a width from about 1 nm to about 200 nm.
 8. The process asdefined in claim 6, wherein said basic calcium phosphate whiskers have aCa/P molar ratio from about 1.35 to about 4.0.
 9. The process as definedin claim 6, wherein said basic calcium phosphate whiskers aresubstantially free of a hydroxyapatite phase.
 10. The process as definedin claim 9, wherein said basic calcium phosphate whiskers comprisetetracalcium phosphate as a major phase.
 11. The process as defined inclaim 6, wherein said whisker-inducing solution in step a) is an acidicaqueous solution, a basic aqueous solution, an organic solvent, orsubstantially pure water.
 12. The process as defined in claim 11,wherein said whisker-inducing solution in step a) is a basic aqueoussolution.
 13. The process as defined in claim 12, wherein said basicaqueous solution is a diammonium hydrogen phosphate, Na₂HPO₄, or K₂HPO₄aqueous solution.
 14. The process as define in claim 13, wherein saidbasic aqueous solution is the diammonium hydrogen phosphate aqueoussolution, and said diammonium hydrogen phosphate aqueous solution has aconcentration of at least 5 wt %, based on the weight of said solution,and the mixing of said TTCP powder with said diammonium hydrogenphosphate aqueous solution in step a) is in a ratio of less than about10 g powder per ml solution.
 15. The process as defined in claim 14,wherein said concentration is 10-60 wt %, and the mixing ratio is lessthan about 5 g powder per ml solution.
 16. The process as defined inclaim 15, wherein said concentration is about 33 wt %, and the mixingratio is about 1 gm TTCP per 13 ml solution.
 17. The process as definedin claim 6, wherein said drying in step b) is carried out by heating themixture resulting from step a) at a temperature less than about 1000° C.18. The process as defined in claim 6, wherein said drying in step b) iscarried out by separating the mixture resulting from step a) and heatingthe separated powder at a temperature of 50-500° C.